A significant subset of both major depressive disorder and bipolar disorder patients
rapidly (within 24 hours) and robustly improves with the chronotherapeutic intervention
of sleep deprivation therapy (SDT). Major mood disorder patients are reported to have
abnormal circadian rhythms including temperature, hormonal secretion, mood, and particularly
sleep. These rhythms are modulated by the clock gene machinery and its products. It
is hypothesized that SDT resets abnormal clock gene machinery, that relapse of depressive
symptoms during recovery night sleep reactivates abnormal clock gene machinery, and
that supplemental chronotherapies and medications can block relapse and help stabilize
circadian-related improvement. The central circadian clock genes, BMAL1/CLOCK (NPAS2),
bind to Enhancer Boxes to initiate the transcription of circadian genes, including
the period genes (per1, per2, per3). It is suggested that a defect in BMAL1/CLOCK (NPAS2) or in the Enhancer Box binding
contributes to altered circadian function associated, in part, with the period genes.
The fact that chronotherapies, including SDT and sleep phase advance, are dramatically
effective suggests that altered clock gene machinery may represent a core pathophysiological
defect in a subset of mood disorder patients.
Key Words
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Article info
Publication history
Published online: August 20, 2012
Accepted:
July 18,
2012
Received in revised form:
July 18,
2012
Received:
July 2,
2012
Identification
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